Lamprecht R, Hazvi S, Dudai Y
Department of Neurobiology, The Weizmann Institute of Science, Rehovot 76100, Israel.
J Neurosci. 1997 Nov 1;17(21):8443-50. doi: 10.1523/JNEUROSCI.17-21-08443.1997.
In conditioned taste aversion (CTA) organisms learn to avoid a taste if the first encounter with that taste is followed by transient poisoning. The neural mechanisms that subserve this robust and long-lasting association of taste and malaise have not yet been elucidated, but several brain areas have been implicated in the process, including the amygdala. In this study we investigated the role of amygdala in general, and the cAMP response element-binding protein (CREB) in the amygdala in particular, in CTA learning and memory. Toward that end, we combined antisense technology in vivo with behavioral, molecular, and histochemical analysis. Local microinjection of phosphorothioate-modified oligodeoxynucleotides (ODNs) antisense to CREB into the rat amygdala several hours before CTA training transiently reduced the level of CREB protein during training and impaired CTA memory when tested 3-5 d later. In comparison, sense ODNs had no effect on memory. The effect of antisense was not attributable to differential tissue damage and was site-specific. CREB antisense in the amygdala had no effect on retrieval of CTA memory once it had been formed, and did not affect short-term CTA memory. We propose that the amygdala, specifically the central nucleus, is required for the establishment of long-term CTA memory in the behaving rat; that the process involves long-term changes, subserved by CRE-regulated gene expression, in amygdala neurons; and that the amygdala may retain some CTA-relevant information over time rather than merely modulating the gustatory trace during acquisition of CTA.
在条件性味觉厌恶（CTA）中，如果生物体首次接触某种味道后紧接着出现短暂中毒，它们就会学会避开这种味道。尽管支持味觉与不适之间这种强烈且持久关联的神经机制尚未阐明，但几个脑区已被认为参与了这一过程，包括杏仁核。在本研究中，我们调查了杏仁核总体上，特别是杏仁核中的环磷酸腺苷反应元件结合蛋白（CREB），在CTA学习和记忆中的作用。为此，我们将体内反义技术与行为、分子和组织化学分析相结合。在CTA训练前数小时，将针对CREB的硫代磷酸酯修饰的寡脱氧核苷酸（ODN）反义物局部微量注射到大鼠杏仁核中，在训练期间会短暂降低CREB蛋白水平，并且在3 - 5天后测试时会损害CTA记忆。相比之下，正义ODN对记忆没有影响。反义物的作用并非归因于不同的组织损伤，且具有位点特异性。杏仁核中的CREB反义物一旦CTA记忆形成，对其提取没有影响，并且不影响短期CTA记忆。我们提出，杏仁核，特别是中央核，是行为大鼠建立长期CTA记忆所必需的；该过程涉及杏仁核神经元中由CRE调节的基因表达所支持的长期变化；并且随着时间推移，杏仁核可能保留一些与CTA相关的信息，而不仅仅是在CTA习得过程中调节味觉痕迹。
